Muscle paralysis and myosin loss in a patient with cancer cachexia.

Cancer cachexia has a significant negative effect on quality of life, survival and the response to treatment. Recent in vitro and experimental animal studies have shown that myosin may be the primary target of the muscle wasting associated with cancer cachexia. In this study, we have extended these analyses to detailed studies of regulation of myofibrillar protein synthesis at the gene level, myofibrillar protein expression and regulation of muscle contraction at the muscle cell level in a 63-year old man with a newly diagnosed small cell lung cancer and a rapidly progressing lower extremity muscle wasting and paralysis. A significant preferential loss of the motor protein myosin together with a downregulation of protein synthesis at the transcriptional level was observed in the patient with cancer cachexia. This had a significant negative impact on muscle fiber size as well as maximum force normalized to muscle fiber cross-sectional area (specific tension).